This is the second revision of application for an exploratory R21 study by a junior clinician-investigator. The goal of the study is to identify conditions under which we can demonstrate stress-induced alprazolam self-administration in patients with post-traumatic stress disorder (PTSD). PTSD is characterized by chronic anxiety and distress following a life-threatening experience. There also is a high frequency of occurrence of comorbid substance abuse and dependence, particularly with alcohol and other sedatives including benzodiazepines. We have strong preliminary data showing that PTSD patients with comorbid alcohol dependence report increased anxiety when listening to a personalized description of their traumatic experience. They also report an increased preference for alcohol and a willingness to spend money to obtain alcohol;however, they do not show an increase in preference for the benzodiazepine, alprazolam. The current application explores the testing of higher doses of alprazolam than previously tested and utilizes experimental conditions we believe are more likely to reveal increased alprazolam preference.
The Specific Aim i s to demonstrate stress-induced alprazolam self-administration in PTSD in response to experimentally- induced traumatic anxiety. We hypothesize that inducing trauma-related anxiety will result in larger increases in alprazolam preference in comparison to neutral control conditions. Using procedures we have applied previously in other studies, patients diagnosed with both PTSD and alcohol dependence will be recruited for a research study requiring hospitalization for seven days. Following a familiarization day, subjects will receive four daily """"""""Sampling"""""""" exposures to double-blind, letter-coded alprazolam or placebo capsules after listening to descriptions of their trauma or descriptions of a personalized, non-arousing situation. Then, on the last two days of the study, subjects will again be re-exposed to the traumatic and non-arousing scenes and be asked to rate their preference for the letter-coded drugs. Preference will be measured by asking subjects to make choices between letter- coded drugs and various amounts of money. The price at which subjects switch their choices from money to drug will be used as a measure of their preference for drug. Our hypothesis will be supported if subjects spend more for alprazolam than placebo following trauma descriptions and if they spend more for alprazolam after trauma descriptions than after descriptions of non-arousing scenes. This study will help us understand the reasons some emotionally traumatized people abuse drugs, including prescription drugs used to control anxiety. This will help guide doctors in safely using medications to calm the anxiety of trauma victims without leading to drug abuse.
